Inhibition of osteosarcoma cell proliferation by the hedgehog-inhibitor cyclopamine
Inhibition of osteosarcoma cell proliferation by the hedgehog-inhibitor cyclopamine
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DOI：
10.1179/joc.2007.19.5.554
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发表时间：
2007-10-01
影响因子：
1.8
通讯作者：
Kurth, A.
中科院分区：
文献类型：
--
作者：
Warzecha, J.;Goettig, S.;Kurth, A.
骨肉瘤是人类最常见的原发性恶性骨肿瘤。尽管OS是化学敏感的，但约30%的患者必须被认为是不良反应者，因此具有令人沮丧的长期预后。Hedgehog（Hh）基因在胚胎发育期间的增殖和分化的信号传导途径中是至关重要的。有证据表明，不受控制的激活这一途径的结果在特定类型的癌症和抑制Hh信号能够抑制肿瘤的生长和诱导细胞凋亡的肿瘤cells.This study investigates the impact of the steroidal alkaloid and Hh-inhibitor cyclopamine on osteosarcoma cells.因此，我们证明了该药物对细胞增殖，细胞周期，细胞死亡以及细胞的代谢的影响。我们在这里证明了cycloparnine对骨肉瘤细胞系HOS，SaOS和OS-KA，一个自我建立的原代骨肉瘤细胞系表现出高的疗效。特别是，cycloparnine能够抑制增殖，促进细胞死亡。我们的研究结果提供了证据的Hh-抑制剂cyclopamine作为一个未来的治疗骨肉瘤的潜力。
Osteosarcomas (OS) are the most frequent primary malignant bone tumors in humans. Even though OS are chemosensitive, about 30% of patients must be considered poor responders and consequently have a dismal long term prognosis. The Hedgehog (Hh) gene is crucial in the signalling pathways of proliferation and differentiation during embryonic development. There is evidence that uncontrolled activation of this pathway results in specific types of cancer and that inhibition of Hh signalling is able to suppress tumour growth and to induce apoptosis of neoplastic cells.This study investigates the impact of the steroidal alkaloid and Hh-inhibitor cyclopamine on osteosarcoma cells. Thus we demonstrate the drug's impact on cellular proliferation, cell cycle cell death as well as the cells' metabolism.We here demonstrate that cycloparnine exhibits a high efficacy against the osteosarcoma cell lines HOS, SaOS and OS-KA, a self-established primary osteosarcoma cell line. In particular, cycloparnine is able to inhibit proliferation and to promote cell death.Our results provide evidence for the potency of the Hh-inhibitor cyclopamine as a future treatment of osteosarcomas.